crossing96/oncoscreening huggingface dataset:
Targeted hotspot profiling reveals a functionally relevant mutation in bladder cancer.	BACKGROUND: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy. METHODS: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients. Somatic variants were identified with GATK Mutect2, annotated with ANNOVAR, and analyzed using maftools. Molecular subtypes were defined through NMF clustering, ssGSEA, and immune deconvolution on TCGA data. Structural and functional impacts of deleterious mutations were assessed through protein modeling, docking, molecular dynamics simulations, and survival analysis. RESULTS: Analysis of somatic variants revealed the presence of frameshift indels (insertions-deletions) and missense SNVs (msSNVs), while T > C and C > T transitions were highly prevalent among the SNVs. The genes that were highly mutated in this series included ATM, APC, STK11, TP53, KIT, MET, ERBB4, RET, KDR, and PIK3CA in each sample. Among these genes, the tumor suppressor gene STK11 was found to be highly deleterious due to a mutation involving phenylalanine to serine substitution at the 255th amino acid position of the STK11 protein. Further, we investigated the effect of somatic mutations in the STK11 gene using different bioinformatics tools. 3D structure analyses and molecular dynamics simulation showed that the mutation occurred within the protein's kinase domain, contributing to the destabilization of the protein's structure; lowered the affinity for ATP binding, and affected the catalytic properties, which may ultimately lead to the loss of its tumor suppressive function. Additionally, mutational signature-based stratification identified 2 molecular subtypes with basal and luminal characteristics. Integrative transcriptomic analysis was performed to characterize these 2 subtypes using publicly available transcriptomic dataset. Despite a lower tumor mutational burden, the basal subtype was significantly associated with immune infiltration within the tumor microenvironment and displayed aggressive and metastatic disease traits. CONCLUSION: Our study highlights STK11 as a key deleterious mutation in Bangladeshi bladder cancer patients, suggesting its potential role in tumor progression and patient prognosis.	bladder
Newly Designed Optical Coherence Tomography Catheter for Optimizing Bladder Cancer Diagnosis and Treatment: Protocol for a Feasibility Study.	BACKGROUND: Bladder cancer diagnosis relies on cystoscopy and transurethral resection of bladder tumor (TURBT) for histopathological evaluation, but this process is time consuming, costly, and subject to variability. Optical coherence tomography (OCT) offers real-time, high-resolution imaging as a potential alternative. OBJECTIVE: This study primarily aims to assess the feasibility of capturing in vivo cross-sectional images of the bladder wall using a novel microelectromechanical systems (MEMS)-based OCT catheter. Secondary objectives include evaluating measurement duration, assessing tumor stage and grade from OCT images in comparison with histopathology, determining the catheter's ability to image resection beds, and comparing OCT-based tumor staging with white light cystoscopy assessments. METHODS: This single-center feasibility study at Amsterdam University Medical Center includes patients undergoing TURBT for suspected bladder tumors. Eligible patients must be aged 18 years or older, have at least 1 cystoscopically accessible tumor, and must be physically fit for TURBT. Exclusion criteria include pregnancy, tumors larger than 2 cm, more than 5 tumors, isolated flat lesions, or tumors solely at the bladder neck. The primary end point assesses the procedural feasibility of OCT imaging, while the secondary end points evaluate tumor staging, grading, and correlation with histopathology. Up to 25 patients will be enrolled, with feasibility achieved if diagnostic images are obtained in more than 60% of the cases. OCT imaging is performed before and after tumor resection, with histopathological results used for comparison. Patients will be monitored for adverse events for 4 weeks after the procedure, after which study participation ends. RESULTS: As of November 2025, 16 participants have been enrolled, and 13 have successfully completed the study procedure. The projected end date of the study is November 2025, and results are expected to be published in March 2026. CONCLUSIONS: This study is expected to provide key insights into the feasibility and clinical utility of the newly developed MEMS-based forward-looking OCT system for real-time bladder imaging during TURBT. This study will lay the groundwork for a larger trial to evaluate its diagnostic accuracy in staging and grading bladder cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT06679920; https://clinicaltrials.gov/study/NCT06679920. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/76644.	bladder
Loss of p190A RhoGAP induces aneuploidy and enhances bladder cancer cell migration and invasion by modulating actin dynamics.	p190A has been studied across various cancer types, and mutation rates of up to 20% were observed in some cancers, supporting the significance of p190A in carcinogenesis. Since the relevance of p190A in bladder cancer has not been addressed so far, we attempted to explore it. Evaluation of TCGA high-throughput sequencing datasets revealed p190A mutations in up to 8% of bladder cancer samples across several studies. Employing immunohistochemistry on tissue microarray that included 202 BC patient samples, we observed that lower p190A expression correlates with increased invasiveness and poorer survival outcomes. These findings suggested that p190A may have a tumor suppressor function in bladder tissue, consistent with its anticipated function in ploidy-control. p190A knockdown resulted in chromosomal instability in ureter-derived epithelial cells with otherwise normal karyotype, supporting its potential involvement in tumorigenesis. Loss-of-function studies in low-invasive bladder RT4 cell line and gain-of-function experiments in two highly invasive bladder cancer cell lines (T24 and BFTC) demonstrated that p190A influences cell migration and invasion in vitro, as determined by scratch assay and Boyden chamber approaches. This conclusion was further validated by ex vivo porcine bladder invasion approach, invadopodia formation, and gelatin degradation assays. Pathway analysis revealed that altered p190A expression influences both the Rho-ROCK-dependent LIMK1-cofilin pathway and the phosphorylation of cortactin by focal adhesion kinase, both of which regulate critical cellular processes such as actin network organization and polarization to facilitate efficient, coordinated cell migration and division. In summary, our results indicate that p190A has a genuine role in controlling cell-ploidy and regulates actin dynamics in the bladder urothelium, while loss of p190A results in genome instability and drives bladder cancer initiation and progression through deregulated actin dynamics.	bladder
Comprehensive analysis of single-cell and bulk transcriptomes reveals key B-cell genes and immune microenvironment regulation in bladder cancer.	BACKGROUND: Bladder cancer is a significant malignancy, for which prognostic prediction and understanding of the tumor immune microenvironment are crucial. B cells play a key regulatory role in this environment, making their study essential for advancing bladder cancer research. METHODS: In this study, a multi-omics analysis strategy combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq was used to establish single-cell transcriptome profiles of tumor tissues from bladder cancer patients, focusing on B-cell populations and their interactions with other cell types in the tumor microenvironment. Large public databases were used to screen for key prognostic genes associated with bladder cancer B cells, and their biomarker expression was verified by in vitro experiments. RESULTS: Based on tumor samples from eight patients with bladder cancer and four normal samples, we selected 84, 967 cells for single-cell sequencing analysis. From these, we identified 10, 967 B cells and identified 508 key genes associated with B cells in bladder cancer from five different B cell subtypes. By integrating a large amount of RNA sequencing data, we identified VCL, FLNA, TAGLN, ACTA2, COL6A2, and CALD1 as potential biomarkers for B-cell-associated bladder cancer, and experimentally verified that these markers were significantly lower in bladder cancer patients than in the normal group, and were effective in predicting the survival rate of the patients and the status of the tumor immune microenvironment. CONCLUSIONS: Using a combination of transcriptomic and experimental validation at single-cell and batch levels, this study provides insights into the key gene signatures of B cells from patients with bladder cancer and their roles in regulating the tumor immune microenvironment, providing new biomarkers and potential therapeutic targets for predicting patient' prognosis and immunotherapy response.	bladder
Natural killer cell infiltration elicits gender-dependent dichotomous clinical outcomes in urothelial carcinoma.	BACKGROUND: Sex differences are a hallmark of urothelial carcinoma (UC), and profoundly influence disease progression and therapeutic outcomes. As critical effector immune cells with intrinsic sexual dimorphism, the contributions of natural killer (NK) cells to this clinical discrepancy remain incompletely understood. METHODS: In this multicohort retrospective study of 885 patients with UC (671 males; 214 females), individuals were stratified into NK(high) and NK(low) subgroups on the basis of immunohistochemical or transcriptomic evaluation. The association of NK cells with clinical outcomes and the tumor immune microenvironment (TME) was systematically assessed across sexes. Single-cell RNA sequencing and flow cytometry were deployed to decipher the functional state of NK cells. RESULTS: Although NK cell infiltration levels were comparable between sexes, their clinical impact was markedly divergent: high NK infiltration conferred a significant survival advantage and superior response to both chemotherapy and immunotherapy exclusively in male patients. Further immune profiling revealed that NK(high) male patients exhibited a coordinated antitumor microenvironment, characterized by immunotype A features, tertiary lymphoid structure formation, and abundant infiltration of dendritic cells and effector T cells. Mechanistically, male-derived NK cells maintained robust cytotoxic and inflammatory programs, whereas female-derived NK cells were polarized toward a stressed, dysfunctional state with decidual-like characteristics. CONCLUSIONS: Altogether, this study establishes NK cells as pivotal mediators of sex differences in UC. The stark contrast in NK cell phenotypes underscores a fundamental sexual dimorphism within the TME, which highlights the urgent need for sex-tailored immunotherapy strategies.	bladder
A CT-based deep learning radiomics model for predicting HER2 expression and prognosis in non-muscle-invasive bladder cancer.	OBJECTIVE: This study aimed to extract radiomics (Rad) and deep learning (DL) features from preoperative CT of patients with Non-Muscle Invasive Bladder Cancer (NMIBC) and develop models incorporating clinical characteristics to assess Human-Epidermal-Growth-Factor-Receptor-2 (HER2) expression status and prognosis in these patients. METHODS: From January 2019 to December 2024, 181 patients with NMIBC were retrospectively enrolled in this study. A deep learning radio-clinical signature model (DLCS) was created by integrating DL score, Rad score, and clinicopathologic features to predict HER2 expression in NMIBC and compared with a deep learning model, a radiomic model, and a Clinical model. An additional model was built to predict Recurrence-Free Survival (RFS) in NMIBC patients. RESULTS: 181 patients with NMIBC were divided into a training cohort (n = 126) and a test cohort (n = 55). The DLCS model achieved the highest area under the curve (AUC) for HER2 prediction in the test cohort (AUC = 0.894 (95% CI: 0.814-0.974)). The univariate and multivariate Cox regression analyses identified both the DL score and Rad score as independent risk factors for RFS (p < 0.05). CONCLUSION: The DLCS model demonstrates good diagnostic performance in predicting HER2 expression, and the prognosis model can stratify the risk of tumor recurrence in patients with NMIBC.	bladder
Utility of node-RADS in preoperatively detecting pelvic lymph node metastasis in bladder cancer.	BACKGROUND: An accurate preoperative nodal staging is crucial for muscle-invasive bladder cancer in risk stratification and treatment decision-making. However, conventional cross-sectional imaging cannot replace pelvic lymph node dissection (PLND) due to accuracy concerns. Recently, Node Reporting and Data System (Node-RADS), a novel structured reporting system for oncological nodal evaluation, has been recently launched. The study is designed to explore the diagnostic utility of Node-RADS in clinical management compared with PLND in bladder cancer. METHODS: The study retrospectively collected patients diagnosed with bladder cancer who had received a preoperative computed tomography scan and subsequent radical cystectomy. Two radiologists independently reviewed the scans according to Node-RADS 1.0 criteria. Nodal staging was histopathologically confirmed by surgical specimens from PLND. The diagnostic performance of Node-RADS was compared both at patient and regional levels. Cohen's kappa was used to exhibit interreader agreement. RESULTS: Lymph node metastasis was found in 22/85 patients by standard PLND. Both Node-RADS score>3 and 4 were suitable diagnostic cutoffs. Node-RADS scores highly correlated with the results of PLND. It exhibited promising diagnostic performance with moderate sensitivity (55.00%), high specificity (85.48%), accuracy (78.05%), and excellent interreader agreement (kappa 0.73-0.95). Whereas, Node-RADS was not observed to have obviously superior diagnostic performance to nodal size criteria in our cohort. CONCLUSION: The study supported the utility of Node-RADS in preoperative pelvic nodal staging, which may assist urologists in selecting appropriate nodal templates. A high positive predictive value enabled the early identification of suitable patients for multimodal treatment to achieve optimal oncological outcomes.	bladder
Second Primary Cancer After Bladder Cancer: A Comprehensive Analysis of a National Cancer Registry.	BACKGROUND: Bladder cancer (BC) is one of the most common cancers and many patients will experience long-term survival. Non-urothelial second primary cancers (SPC) relatively frequently occur in the population of BC survivors. METHODS: Czech National Cancer Registry was the principal data source for this study. The risk of development of non-urothelial SPC after BC was assessed by the standardized incidence ratio (SIR). The standardized mortality ratio (SMR) was utilized to determine the risk of death from SPC following BC. RESULTS: Of the total of 61,314 patients with BC, a cohort of 12,645 survivors diagnosed with a SPC were analyzed. Compared to the general population, the SIR of neoplasia was significantly increased in BC survivors, with a SIR of 1.75 (95% confidence interval [CI] 1.72-1.78) for all cancers, especially during the first 5 years after BC diagnosis. The SMR was increased in BC survivors (1.25; 95% CI 1.21-1.29) for all cancers. Lung cancer frequently occurred as a SPC and was associated with high mortality in BC survivors. BC survivors also had a higher risk of laryngeal cancer and other cancers known to be strongly associated with smoking, but also of soft tissue tumors, colorectal cancer, chronic lymphocytic leukemia, and thyroid cancer. CONCLUSIONS: The present large registry-based study shows that BC survivors have a significantly higher risk of being diagnosed with another primary cancer compared to the general population, especially during the first 5 years after BC diagnosis. In addition to smoking-related cancers, increased incidence of some cancers not known to be associated with smoking was observed.	bladder
Molecular subtyping of advanced bladder cancer patients and patient-derived organoids based on a 3-marker immunohistochemistry approach to evaluate chemotherapy sensitivity.	BACKGROUND: Bladder cancer is among the top ten most common cancers globally and one of the most expensive to treat, primarily due to high recurrence rates stemming from significant heterogeneity and mutational rates. The standard treatment, cisplatin-based combination chemotherapy, yields only 40-56% clinical responses, highlighting the need for improved patient stratification to enable precision treatments. Currently, in general practice patient stratification is based on physical fitness and immunohistopathological characterization. While molecular subtyping has traditionally relied on RNA-sequencing, this method is clinically impractical due to cost and often lacking direct sensitivity correlation. Therefore, we aim to develop an immunohistochemistry-based classification system for the major bladder cancer subtypes. METHODS AND PATIENT SUMMARY: We used the log10 IHC ratios of 3 markers to classify major bladder cancer subtypes. We applied this subtyping in 3 patient cohorts. First on a tissue microarray cohort (n = 53) from cystectomy treated MIBC patients. Furthermore, a cisplatin-based neoadjuvant chemotherapy cohort with pre- and post-treatment tissues (n = 18). Finally, patient derived bladder cancer organoid cohort (n = 8) for direct subtype specific drug sensitivity testing. KEY FINDINGS AND LIMITATIONS: Our findings reveal that the classification system offers a valuable approach for subtyping patients individually, in cohorts and in patient-derived organoids (n = 8 distinct organoid lines). Second, this classification system allows detection of subtype changing in patients undergoing neoadjuvant chemotherapy. Furthermore, the classification system effectively distinguishes between significantly (P = 4.07e-10) cisplatin-sensitive (basal-like) and cisplatin-resistant (luminal-like) subtypes in bladder cancer organoids and is hypothesis generating. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our findings suggest that our 3-marker classification system could be valuable as method in future BC patient subtyping for clinical stratification of patients undergoing cisplatin-based treatment.	bladder
The association between digestion-resistant and bioactive peptide content of dairy products and bladder cancer: a case-control study.	BACKGROUND: Bladder cancer is the sixth most common cancer worldwide. Bioactive peptides (BP) are digestion-resistant (enzymatically stable) and absorbable fragments that exert physiological functions in the body. We conducted this case-control study to examine the association between dairy-derived BPs and bladder cancer. METHODS: The present case-control study (103 cases and 200 controls) was a hospital-based investigation conducted in three referral hospitals in Tehran, Iran. Dietary intake was assessed using a validated 168-item Food Frequency Questionnaire (FFQ). Intake of BPs was estimated based on dairy product consumption recorded in the FFQ. Logistic regression analysis was used to examine the association between the content of digestion-resistant BPs in dairy products and the odds of bladder cancer. RESULTS: After adjusting confounding factors, it was observed that the odds of bladder cancer were significantly lower in the second and last tertiles (T) of total peptide intake from dairy products compared to the first tertile (T(2): odds ratio (OR) = 0.285; 95% confidence interval (CI): 0.116-0.699, T(3): OR = 0.130; 95% CI: 0.032-0.527). Additionally, in the adjusted model, a significant inverse association was found between other dairy-derived peptides and the odds of bladder cancer. CONCLUSIONS: The findings suggest a potential inverse relationship between milk-derived BPs and bladder cancer risk, which warrants further investigation in longitudinal or interventional studies. However, further studies are needed to elucidate the biological properties and mechanism of action of milk-derived BPs.	bladder
TPI1 enhances gemcitabine resistance in bladder cancer by promoting autophagy through activating Beclin-1.	The persistent issues of drug resistance and tumor recurrence remain major challenges in bladder cancer (BCa) treatment, severely impacting patient outcomes. In this study, we found that Triosephosphate isomerase 1 (TPI1) plays a crucial role in influencing gemcitabine (Gem) resistance in BCa. TPI1 is significantly upregulated in Gem-resistant BCa tissues, and the knockdown of TPI1 markedly increases Gem sensitivity and chemotherapy-induced apoptosis both in vivo and in vitro. Meanwhile, the same was validated in Gem-resistant strains. Mechanistically, transcriptome sequencing and transmission electron microscopy, among others, revealed that TPI1 promoted Gem-associated autophagy. Furthermore, mass spectrometry and co-immunoprecipitation assays demonstrated that TPI1 directly binds to the BH3 domain of Beclin-1. This interaction competitively disrupts the binding between Bcl-2 and Beclin-1, thereby relieving Bcl-2-mediated inhibition of Beclin-1. Furthermore, the interaction between TPI1 and Beclin-1 promotes the formation of PIK3C3-C1, which in turn enhances the interaction between PIK3C3-C1 and the ULK1 complex, thereby increasing the phosphorylation of Beclin-1 at Ser15. In addition, TPI1 also enhanced mitochondrial autophagy induced by Gem in BCa cells and tissues. Importantly, a transcription factor, c-Myc, that regulates TPI1 expression was also identified, and dual luciferase and Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis showed that c-Myc binds primarily to the promoter region of TPI1. Our results suggest that TPI1 plays an important role in regulating the formation of autophagic complexes, and that promoting autophagy significantly increased Gem resistance in BCa.	bladder
Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.	Extracellular vesicles (EVs) are critical mediators of intercellular communication within the tumour microenvironment and play a significant role in drug resistance. We aimed to investigate the mechanisms underlying gemcitabine (GCB) resistance in bladder cancer. GCB-resistant bladder cancer cells exhibited dysregulation of nucleoside-metabolizing enzymes and transporters. Characterization of EV subpopulations derived from GCB-resistant cells revealed their ability to transfer drug-resistant phenotypes to naïve cancer cells by modulating intracellular levels of nucleoside metabolic proteins and transporters. Proteomic and transcriptomic analyses identified the histone protein H3.2 and its corresponding transcript, H3C14, as key regulators in the transmission of GCB resistance. Notably, H3C14 overexpression in resistant cells restored GCB sensitivity, whereas its knockdown induced GCB resistance. Rab27A-mediated biogenesis and secretion emerged as a crucial mechanism regulating EV release and H3C14 excretion in GCB-resistant cells. A specific EV subpopulation enriched in CD147 and LAMB1-referred to as Excretion EVs-carried H3.2 (H3C14) but did not induce GCB resistance in recipient cells, suggesting their primary role in eliminating proteins associated with tumour progression and drug resistance. These findings highlight the role of EV-mediated H3C14 excretion in regulating GCB resistance and suggest potential therapeutic strategies targeting EV pathways to overcome drug resistance in bladder cancer.	bladder